|Knowles, Donald - Don|
Submitted to: American Journal of Pathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/7/2004
Publication Date: 4/1/2005
Citation: Herrmann, L.M., Cheevers, W.P., Davis, W.C., Knowles, Jr., D.P., O'Rourke, K.I. 2005. CD21 positive follicular dendritic cells: A possible source of PrPSc in lymph node macrophages of scrapie-infected sheep. American Journal of Pathology. 162(4):1075-1081. Interpretive Summary: Natural sheep scrapie is part of a group of neurodegenerative diseases called transmissible spongiform encephopathies (TSE's) and continues to be spread in flocks in the United States. The presence of prion protein (PrPSc) in germinal centers of lymphoid tissues of scrapie-infected sheep is a marker for scrapie. But, little information exists regarding the specific cell types in lymphoid tissue that accumulate PrPSc. Using dual immunohistochemistry, follicular macrophages cells involved in the immune response of lymph nodes from scrapie-infected sheep were found to accumulate PrPSc.
Technical Abstract: Natural sheep scrapie is a prion disease characterized by the accumulation of PrPSc in brain and lymphoid tissues. Previous studies suggested that lymph node macrophages and follicular dendritic cells (FDC) accumulate PrPSc. In this study, lymph nodes were analyzed for the presence of PrPSc and macrophage or FDC markers using dual immunohistochemistry. A mAb to the C-terminus of PrP reacted with CD172a+ macrophages and CD21+ FDC processes in secondary follicles. However, a PrP N-terminus specific mAb reacted with CD21+ FDC processes but not CD172a+ macrophages in secondary follicles. Neither the PrP N-terminus nor C-terminus specific mAb reacted with CD172a+ macrophages in the medulla. These results indicate that lymph node follicular macrophages acquire PrPSc by phagocytosis of CD21+ FDC iccosomes. The results also suggest that follicular macrophages have proteases that process full length PrPSc to N-terminally truncated PrPSc.